OBJECTIVE: To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union. METHODS: The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union. RESULTS: Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity. CONCLUSION TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.
Humans ; Fracture Healing/physiology* ; Brain Injuries/metabolism* ; Brain Injuries, Traumatic ; Fractures, Bone ; Osteogenesis

Even though retinal images of objects change their locations following each eye movement, we perceive a stable and continuous world. One possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal information. There have been several proposals on how this may be done, including eye-position modulation (gain fields) of retinotopic receptive fields (RFs) and craniotopic RFs. In the present study, we investigated coordinate systems used by RFs in the lateral intraparietal (LIP) cortex and frontal eye fields (FEF) and compared the two areas. We mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate representation. The same recording and analysis procedures were applied to the two brain areas. We found that, in both areas, RFs were distributed from retinotopic to craniotopic representations. There was no significant difference between the distributions in the LIP and FEF. Only a small fraction of neurons was fully craniotopic, whereas most neurons were between the retinotopic and craniotopic representations. The distributions were strongly biased toward the retinotopic side but with significant craniotopic shifts. These results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF, and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.
Animals ; Macaca ; Visual Fields ; Frontal Lobe/physiology* ; Eye Movements ; Brain

In this study, we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions. We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful (or non-painful) stimulation to Asian and White models' faces to trigger painful (or neutral) expressions. We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100 ms-200 ms, in the orbitofrontal and subgenual anterior cingulate cortices at 150 ms-200 ms, in the anterior cingulate cortex around 250 ms-350 ms, and in the temporoparietal junction and middle temporal gyrus around 600 ms after video onset. Perceived dynamic pain in White models modulated activities in the visual, anterior cingulate, and primary sensory cortices after 500 ms. Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race (vs other-race) individuals in dynamic painful situations.
Adult ; Humans ; Brain Mapping ; Pain ; Empathy ; Racism ; Gyrus Cinguli/physiology* ; Magnetic Resonance Imaging ; Brain/physiology*

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins

OBJECTIVES: To analyze the effect of acupuncture at the acupoints for Yizhi Tiaoshen (benefiting the intelligence and regulating the spirit) on the functional connectivity between the hippocampus and the whole brain in the patients with Alzheimer's disease (AD), and reveal the brain function mechanism of acupuncture in treatment of AD using resting state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty patients with mild to moderate AD were randomly divided into an acupuncture + medication group (30 cases, 3 cases dropped out) and a western medication group (30 cases, 2 cases dropped out). In the western medication group, the donepezil hydrochloride tablets were administered orally, 2.5 mg to 5 mg each time, once daily; and adjusted to be 10 mg each time after 4 weeks of medication. Besides the therapy as the western medication group, in the acupuncture + medication group, acupuncture was supplemented at the acupoints for Yizhi Tiaoshen, i.e. Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Xuanzhong (GB 39). The needles were retained for 30 min in one treatment, once daily; and 6 treatments were required weekly. The duration of treatment was 6 weeks in each group. The general cognitive function was assessed by the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive part (ADAS-Cog) before and after treatment in the two groups. Using the rs-fMRI, the changes in the functional connectivity (FC) of the left hippocampus and the whole brain before and after treatment were analyzed in the patients of the two groups (11 cases in the acupuncture + medication group and 12 cases in the western medication group). RESULTS: After treatment, compared with those before treatment, MMSE scores increased and ADAS-Cog scores decreased in the two groups (P<0.05); MMSE score was higher, while the ADAS-Cog score was lower in the acupuncture + medication group when compared with those in the western medication group (P≤0.05). After treatment, in the western medication group, FC of the left hippocampus was enhanced with the left fusiform gyrus, the inferior frontal gyrus of the left triangular region, the bilateral superior temporal gyrus and the right superior parietal gyrus (P<0.05), while FC was weakened with the left inferior temporal gyrus, the left middle frontal gyrus and the right dorsolateral superior frontal gyrus when compared with that before treatment (P<0.05). After treatment, in the acupuncture + medication group, FC of the left hippocampus was increased with the right gyrus rectus, the left inferior occipital gyrus, the right superior temporal gyrus and the left middle occipital gyrus (P<0.05), and it was declined with the left thalamus (P<0.05) when compared with those before treatment. After treatment, in the acupuncture + medication group, FC of the left hippocampus was strengthened with the bilateral inferior temporal gyrus, the bilateral middle temporal gyrus, the right gyrus rectus, the bilateral superior occipital gyrus, the left lenticular nucleus putamen, the left calcarine fissure and surrounding cortex, the inferior frontal gyrus of the left insulae operculum, the left medial superior frontal gyrus and the right posterior central gyrus (P<0.05) compared with that of the western medication group. CONCLUSIONS Acupuncture at the acupoints for Yizhi Tiaoshen improves the cognitive function of AD patients, and its main brain functional mechanism is related to intensifying the functional connectivity of the left hippocampus with the default network (inferior temporal gyrus, middle temporal gyrus and superior frontal gyrus, gyrus rectus), as well as with the sensory (posterior central gyrus) and visual (calcarine fissure and surrounding cortex and superior occipital gyrus) brain regions.
Humans ; Acupuncture Points ; Alzheimer Disease/therapy* ; Magnetic Resonance Imaging ; Brain/physiology* ; Acupuncture Therapy ; Hippocampus/diagnostic imaging*

Humans ; Blood Pressure/physiology* ; Cohort Studies ; Patient Discharge ; Ischemic Stroke ; Stroke ; Brain Ischemia ; Diabetes Mellitus ; Hypertension

The aim of the present study was to explore the specific pattern of brain deactivation elicited by painful stimuli, in contrast with that elicited by tactile stimuli. Functional magnetic resonance imaging (fMRI) data were collected from 62 healthy subjects under painful and tactile stimuli with varying intensities. The brain deactivations under different conditions were identified using the general linear model. Two-way analysis of variance (ANOVA) was performed to test whether there was a significant interaction between perceived stimulus intensity (factor 1: high intensity, low intensity) and stimulus modality (factor 2: pain, touch) on the brain deactivations. The results showed that there were significant interactions between stimulus intensity and stimulus modality on the deactivations of left medial superior frontal gyrus, left middle occipital gyrus, left superior frontal gyrus and right middle occipital gyrus (P < 0.05, Cluster-level FWE). The deactivations induced by painful stimuli with low perceived intensity (β = -3.38 ± 0.52) were significantly stronger than those induced by painful stimuli with high perceived intensity (β = -1.22 ± 0.54) (P < 0.001), whereas the differences between the deactivations induced by tactile stimuli with different perceived intensities were not statistically significant. In addition, there were no significant differences between the deactivations elicited by painful and tactile stimuli with the same stimulus intensities. These results suggest that there is a specific relationship between the deactivations induced by painful stimuli in multiple brain regions (such as the left medial superior frontal gyrus) and the stimulus intensity, providing evidence for a deeper understanding of the brain mechanisms underlying pain perception.
Humans ; Touch/physiology* ; Physical Stimulation/methods* ; Pain ; Brain/physiology* ; Magnetic Resonance Imaging/methods* ; Brain Mapping

Aging is a natural process accompanied with a progressive deterioration of cognitive functions. With an aging population, more and more elderly people are suffering from cognitive impairment. Previous studies have paid more attention to the impact of inflammation and oxidative stress on cognitive function during aging. Recently, it has been discovered that neurovascular coupling (NVC), a mechanism regulating cerebral blood flow, may play a significant role in aging-related cognitive impairment. NVC responses regulate the supply of energy substances and oxygen during brain activity, which in turn enhances cognitive function. However, as people grow older, NVC responses gradually weaken, which may be one of the mechanisms underlying aging-induced cognitive impairment. Given the important role of NVC responses in the brain, it is necessary to search for intervention methods that can improve NVC responses and promote cognitive function. Exercise is an effective means to delay aging and improve cognitive function. It also has a certain promoting effect on NVC responses. This article reviews the regulatory mechanisms of NVC responses, the relationship between NVC responses and cognitive function, and explores the effects of aging and exercise intervention on NVC responses, hoping to provide new research ideas for exercise intervention to improve NVC responses and promote cognitive function in the elderly.
Humans ; Aged ; Neurovascular Coupling/physiology* ; Aging ; Cerebrovascular Circulation/physiology* ; Cognition ; Brain